Zebinix® (eslicarbazepine acetate) Receives Positive CHMP Opinion as Once-daily Monotherapy for Newly Diagnosed Focal-onset Epilepsy

PORTO, Portugal and HATFIELD, England, March 28, 2017 /PRNewswire/ --

FOR EMEA MEDIA ONLY - NOT FOR SWISS/AUSTRIAN JOURNALISTS

Efficacy and safety/tolerability of once-daily eslicarbazepine acetate in the monotherapy setting demonstrated in a Phase III, double-blind, active-controlled trial^[1],[2]

Bial and Eisai today announce that Zebinix^® (eslicarbazepine acetate) has received a positive opinion for use as a once-daily monotherapy to treat adults with newly-diagnosed focal onset epilepsy from The European Medicine Agency's Committee for Medicinal Products for Human Use (CHMP).

Eslicarbazepine acetate is currently indicated in Europe as adjunctive therapy in adults, adolescents and children aged above 6 years, with partial-onset (focal) seizures with or without secondary generalisation.^[3]

The CHMP based its decision on positive results from a Phase III study in a monotherapy setting which showed that eslicarbazepine acetate was proven to be non-inferior to controlled-release carbamazepine in patients with newly diagnosed focal onset seizures.^[1],[4]

The Phase III, randomised, double-blind, active-controlled, non-inferiority study^[1] (Study 311) compared once-daily eslicarbazepine acetate as monotherapy treatment for newly diagnosed adults with focal-onset seizures to twice-daily, controlled-release carbamazepine. The primary endpoint was the proportion of patients seizure-free for the entire 26-week evaluation period.^[1]

815 eligible patients were randomised for the trial. In the per-protocol (PP) population (n=785), seizure freedom rates with eslicarbazepine acetate were similar to those observed with controlled-release carbamazepine in eligible patients. The data show that 71.1% (n=276) of patients for eslicarbazepine acetate and 75.6% (n=300) of patients for controlled-release carbamazepine were seizure-free for six months or more, at the last evaluated dose (average risk difference -4.28%, 95% CI -10.3, 1.74%). The one-year seizure-freedom rate at the last evaluated dose was 64.7% (n=251) on eslicarbazepine acetate and 70.3% (n=279) on controlled-release carbamazepine (average risk difference: -5.46%; 95%CI: -11.88, 0.97%).^[1]

"This CHMP decision, with the promise it brings of a new treatment option for patients is very welcome. Around 60 per cent of patients with epilepsy have focal seizures, and we also know that adherence to treatment is better with a once-daily monotherapy." explains Eugen Trinka, Professor and Chair of Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria.

"This is important news for people with focal epilepsy who may now be able to benefit from a once-daily monotherapy treatment as soon as they are diagnosed. It is a relevant milestone in the development program of eslicarbazepine acetate and we are delighted that we may now be able to offer this treatment option for patients with focal epilepsy across Europe," comments António Portela, CEO of Bial, Porto, Portugal.

A safety analysis^[2] of the same study showed the side effects of eslicarbazepine acetate were mostly of mild intensity, and consistent with the known safety profile. Incidence rates of treatment emergent adverse events (TEAEs) were similar but slightly higher in patients receiving controlled-release carbamazepine (77.7%) (n=320) versus eslicarbazepine acetate (75.3%) (n=302). Possibly-related TEAEs were also slightly higher at 49.5% (n=204) for controlled-release carbamazepine compared with 41.1% (n=165) for eslicarbazepine acetate, for serious possibly-related TEAEs (2.7% vs 2.0%) (n=11 vs n=8), and for TEAEs leading to withdrawal (18.0% vs 13.5%) (n=74 vs n=54). The most frequently reported possibly-related TEAEs for eslicarbazepine acetate were headache, dizziness, nausea, fatigue, and somnolence.^[2]

"This positive opinion from the CHMP reinforces Eisai's commitment to researching and developing neurological treatment options that have the potential to help people manage their condition. We are pleased that this decision means patients in Europe who experience epilepsy will have a broader range of treatment options available," comments Neil West, Vice President EMEA, Global Neurology Business Unit at Eisai.

The continued development of eslicarbazepine acetate underscores Bial's and Eisai's commitment to developing and delivering highly beneficial new treatments to help improve the lives of people with epilepsy.

Notes to Editors 

About Zebinix^®(eslicarbazepine acetate)

Eslicarbazepine acetate is a voltage-gated sodium channel blocker. It selectively targets the slow inactivated state of the sodium ion channel (which have been implicated in the pathogenesis of epilepsy), preventing its return to the active state, and thereby reduces repetitive neuronal firing.^[5] Further, eslicarbazepine acetate does not inhibit potassium efflux, which may reduce the potential for repetitive neuronal firings.^[6] The efficacy of eslicarbazepine acetate was demonstrated in an initial proof-of-concept phase II study^[7] and three subsequent phase III randomised, placebo controlled studies in 1,049 people with refractory partial onset seizures.^[8],[9],[10]

Eslicarbazepine acetate is currently marketed in Europe and Russia by Bial and by Bial's licensee, Eisai Europe Limited, a European subsidiary of Eisai Co Ltd under the trade name Zebinix^® or Exalief^®. In the United States and Canada eslicarbazepine acetate (tradename Aptiom^®) is marketed by Sunovion Pharmaceuticals Inc under an exclusive license from Bial.

About Epilepsy  

Epilepsy is one of the most common neurological conditions in the world, affecting approximately 6 million people in Europe, and an estimated 50 million people worldwide.^[11] Epilepsy is a chronic disorder of the brain that affects people of all ages. It is characterised by abnormal discharges of neuronal activity which causes seizures. Seizures can vary in severity, from brief lapses of attention or jerking of muscles, to severe and prolonged convulsions. Depending on the seizure type, seizures may be limited to one part of the body, or may involve the whole body. Seizures can also vary in frequency from less than one per year, to several per day. Epilepsy has many possible causes but often the cause is unknown.

About Bial  

Founded in 1924, BIAL's mission is to discover, develop and provide therapeutic solutions within the area of health. In recent decades, BIAL has strategically focused on quality, innovation and internationalization.

Bial is strongly committed to therapeutic innovation, investing more than 20 per cent of its turnover in Research and Development (R&D) every year.

Bial has established an ambitious R&D program centered on the neurosciences and cardiovascular system. The company expects to introduce more new medicines to the market in the next years, strengthening its international presence based in its own innovative medicines and accomplishing the company's purpose of "Caring for your Health."

For more information about Bial, please visit www.bial.com.

About Eisai Co Ltd  

Eisai Co Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realise our hhc philosophy by delivering innovative products in multiple therapeutic areas with high unmet medical needs, including Oncology and Neurology. 

As a global pharmaceutical company, our mission extends to patients around the world through our investment and participation in partnership-based initiatives to improve access to medicines in developing and emerging countries.

For more information about Eisai Co., Ltd., please visit http://www.eisai.com

References 

1. Ben-Menachem E, et al. Efficacy of eslicarbazepine acetate versus controlled-release carbamazepine as monotherapy in patients with newly diagnosed partial-onset seizures; European Congress on Epileptology 2016: Abstract #0002 

2. Kowacs P, et al. Safety and tolerability of eslicarbazepine acetate as monotherapy in patients with newly diagnosed partial-onset seizures. Presented at EAN 2016; abstract #P32045 

3. Zebinix® (eslicarbazepine acetate) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000988/WC500047225.pdf Accessed March 2017.

4. Trinka E, et al. Safety and tolerability of eslicarbazepine acetate as monotherapy in patients with newly diagnosed partial-onset seizures; European Congress on Epileptology 2016: Abstract #P615 

5. Hebeisen S, et al. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology 2015; 89:122-35 

6. Soares-da-Silva P, et al. Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action. Pharmacol Res Perspect. 2015; 3:e00124 

7. Elger C, et al. Eslicarbazepine acetate: A double-blind, add-on, placebo-controlled exploratory trial in adult patients with partial-onset seizures. Epilepsia 2007; 48:497-504 

8. Elger C, et al. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: A randomised, double-blind, placebo-controlled, parallel-group phase III study. Epilepsia. 2009;50:454-63 

9. Ben-Menachem E, et al. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. Epilepsy Res. 2010;89(2-3):278-85 

10. Gil-Nagel A, et al. Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures. Acta Neurol Scand. 2009; 120:281-87

11. Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. Available at: http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf Accessed March 2017

March 2017
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